Characterizing semen abnormality male infertility using non-targeted blood plasma metabolomics
Characterizing semen abnormality male infertility using non-targeted blood plasma metabolomics
复制标题
使用非靶向血浆代谢组学表征精液异常男性不育症
DOI：
10.1371/journal.pone.0219179
复制
发表时间：
2019-07-05
期刊：
影响因子：
3.7
通讯作者：
Wang, Yang
中科院分区：
文献类型：
--
作者：
Ma, Pan;Zhang, Zhimin;Wang, Yang
精液异常（SA）男性不育已成为世界性的生殖健康问题。侵入性测试（例如，睾丸活组织检查）和劳动密集型的精液采集方法严重阻碍了男性不育症的诊断。此外，男性不育的发病机制和生物学解释仍然不清楚。本研究采用GC-MS对84例精液异常患者（畸形精子症（TE）21例，弱精子症（AS）23例，少精子症（OL）20例，无精子症（AZ）20例）和29例正常对照者（HC）的精液进行了分析。通过多变量统计方法（偏最小二乘判别分析，PLS-DA）和单变量统计方法（方差分析，ANOVA）获得23个生物标志物，并将TE与HC、AS与HC、OL与HC和AZ与HC进行比较。基于这些生物标志物，最相关的途径主要与碳水化合物、氨基酸和脂质的代谢相关。SA男性不育的主要代谢改变包括能量相关代谢水平的增加，如三羧酸循环、丙酮酸代谢、乙醛酸和二羧酸代谢、甘氨酸、丝氨酸、苏氨酸代谢和饱和脂肪酸代谢。此外，谷胱甘肽代谢水平的增加与氧化应激有关。最后，观察到精氨酸和脯氨酸代谢以及磷酸肌醇代谢水平降低。总之，血浆代谢组学是强大的特征SA男性不育症的代谢紊乱。从代谢途径分析，能量产生、氧化应激和精子发生过程中释放的酶是SA男性不育的主要原因。
Semen abnormality (SA) male infertility has become a worldwide reproductive health problem. The invasive tests (e.g., testicular biopsy) and labor-intensive methods of semen collection severely inhibit diagnosis of male infertility. In addition, the pathogenesis and biological interpretation of male infertility are still obscure. In this report, a total of 84 semen abnormality (SA) patients, diagnosed as teratozoospermia (TE, n = 21), asthenozoospermia (AS, n = 23), oligozoospermia (OL, n = 20), azoospermia (AZ, n = 20), and age-matched healthy controls (HC, n = 29) were analyzed by GC-MS for discrimination analysis and discovery of potential biomarkers. Twenty-three biomarkers were obtained by multivariate statistical method (partial least squares-discriminant analysis, PLS-DA) and univariate statistical method (analysis of variance, ANOVA) with comparisons of TE versus HC, AS versus HC, OL versus HC and AZ versus HC. Based on those biomarkers, the most relevant pathways were mainly associated with the metabolism of carbohydrates, amino acids, and lipids. The principal metabolic alternations in SA male infertility included increased levels of energy-related metabolisms, such as tricarboxylic acid cycle, pyruvate metabolism, glyoxylate and dicarboxylate metabolism, glycine, serine, threonine metabolism and saturated fatty acid metabolism. Furthermore, increased levels of glutathione metabolism were related to oxidative stress. Finally, decreased levels of arginine and proline metabolism and inositol phosphate metabolism were observed. In conclusion, blood plasma metabolomics is powerful for characterizing metabolic disturbances in SA male infertility. From metabolic pathway analysis, energy production, oxidation stress and the released enzyme during spermatogenesis take the primary responsibilities for SA male infertility.